Renal Transplantation (Medical)

TREATMENT

Medical Care: The primary goal of short-term and long-term medical follow-up is enabling surveillance for signs and symptoms of renal allograft dysfunction.

Renal parenchymal dysfunction has many etiologies. The clinical manifestation is typically an increase in serum creatinine. Causes are numerous, and the differential diagnosis must be approached systematically.

The greatest considerations are rejection, nephrotoxicity of calcineurin inhibitors, and recurrence of native kidney disease. The time interval between transplantation and the rise in serum creatinine often is helpful to determine the etiology graft dysfunction.

• Delayed graft function immediately posttransplantation usually is due to acute tubular necrosis (ATN). Frequency is variable among the different transplant centers and approximates roughly 20-30% of cadaver transplants.

• The nephrotoxicity of calcineurin inhibitors, cyclosporine and tacrolimus, is dose related. Occasionally, performing a renal allograft biopsy is necessary if the serum creatinine does not respond to a reduction in dose.

• Hemolytic uremic syndrome (HUS) has an unknown etiology, but it seems to be associated with endothelial injury associated with calcineurin inhibitors and the occurrence of CMV. Laboratory evaluation showing diminished platelet count, anemia, reduced haptoglobin levels, rising lactic dehydrogenase (LDH) levels, and a peripheral blood smear with schistocytes is consistent with the diagnosis. The definitive diagnosis is made with the aid of renal allograft biopsy showing glomerular microthrombi.

• Recurrent renal disease in patients who have had kidney transplants accounts for less than 2% of all graft losses, though it affects as many as 10% of transplant recipients. A few diseases have a high risk of renal allograft loss, such as focal segmental glomerulosclerosis, HUS oxalosis, and membranoproliferative glomerulonephritis. Diabetic nephropathy can recur in renal allografts, but the time to onset is similar to that seen in native kidneys and is an uncommon cause of graft loss.

• Rejection

• Hyperacute rejection of the renal allograft happens within hours of the transplant, and it occurs when circulating, preformed, cytotoxic, antidonor antibodies directed to the ABO blood group antigens or to the donor HLA class I antigens are present. No treatment exists, and nephrectomy is indicated.

• Accelerated acute rejection is a very early, rapidly progressive, aggressive rejection reaction. It can occur within the first week of transplantation. Immediate therapy with anti–T-cell antibodies and pulse corticosteroids may reverse the process. Approximately 50% of cases can be salvaged.

• Acute tubular interstitial cellular rejection is the most common type of rejection reaction with an incidence of approximately 20-25%. Typically, it occurs between 1-3 months posttransplant. It is T-cell mediated, and injury is directed to the renal tubules. The criterion standard for diagnosis is renal allograft biopsy. Mild rejections may be successfully reversed with corticosteroids alone, whereas moderate or severe rejections may require the use of anti–T-cell antibodies, either polyclonal or monoclonal.

• Chronic rejection is a slow and progressive deterioration in renal function characterized by histologic changes involving the renal tubules, capillaries, and interstitium. The precise mechanism of this disease is poorly defined and is an area of intense study. Application of conventional antirejection agents, such as corticosteroids or anti–T-cell antibodies, does not appear to alter the progressive course. Unfortunately, this is a major cause of kidney allograft loss, occurring later than 2 years posttransplant.

Surgical Care:

• Wound complications: In patients who have had transplants, risk factors for and the morbidity of wound complications are significant.

• Bleeding: Kidney transplantation is a vascular surgery procedure; however, it is not an operation associated with much blood loss. Postoperatively, a life-threatening bleeding complication is very rare but could result from rupture of the arterial anastomosis from a mycotic aneurysm.

• Vascular thrombosis: Acute arterial thrombosis occurs in 1% of all kidney transplants. Salvage of the renal allograft is possible if diagnosed within the first one half hour of occurrence (during recovery in the postanesthesia recovery room). Rarely, venous thrombosis occurs. If it occurs, the kidney usually is unsalvageable. The cause often is never satisfactorily identified.

• Urine leak: Leaks occur at the ureterovesical junction or through a ruptured calyx secondary to acute ureteral obstruction. Often, the etiology of early urine leak is due to necrosis of the tip of the ureter. Urine leaks manifest as diminished urine output, an increase in creatinine, and lower abdominal or suprapubic discomfort. Repair employing minimal intervention may be attempted with either a percutaneous nephrostomy and drainage with internal stenting or through a cystoscopic retrograde approach. More aggressive treatment involves operative intervention with reimplantation of the ureter or a ureteroureterostomy, utilizing the ipsilateral native ureter.

• Ureteral stenosis and obstruction: This is a relatively late complication, occurring months or years posttransplant, that could result from ischemia of the ureter or a tight ureteroneocystostomy. Ureteral stenosis is manifested by elevated creatinine and hydronephrosis.

• Lymphocele: This is a circumscribed collection of retroperitoneal lymph that originates from lymphatic vessels about the iliac vasculature and the hilum of the kidney. Significant secondary problems may arise if external compression of the iliac vein (causing leg swelling and discomfort) or compression of the transplant ureter (causing hydronephrosis and renal dysfunction) occurs. The standard principal is that intraperitoneal drainage of the lymphocele should be accomplished with either a laparoscopic or an open surgical approach, with marsupialization of the edges of the lymphocele.

MEDICATION

Medications are used in renal transplantation for immunosuppression.

All kidney transplant recipients require life-long immunosuppression to prevent a T-cell, alloimmune rejection response. Several new immunosuppressive agents have been approved by the Federal Drug Administration (FDA), and several others currently are in clinical trials.

There are 2 broad classifications of immunosuppressive agents, intravenous induction of antirejection agents and maintenance immunotherapy agents. No consensus exists about which is the single best immunosuppressive protocol, and each transplant program utilizes various combinations of agents slightly differently.

The goals are to prevent acute and chronic rejection, to minimize drug toxicity and rates of infection and malignancy, and to achieve the highest possible rates of patient and graft survival.

Drug Category: Antirejection induction agents -- Induction immunotherapy consists of a short course of intensive treatment with intravenous agents. Antilymphocyte antibody induction therapeutics are varied and include polyclonal antisera, mouse monoclonals, and so-called humanized monoclonals. Polyclonal antisera, such as antilymphocyte globulin (ALG), antilymphocyte serum (ALS), and antithymocyte globulin (ATG), are equine, goat, or rabbit antisera directed against human lymphoid cells. The effect is to significantly lower and almost abolish the circulating lymphoid cells that are critical to the rejection response.